ProjectSummary Parkinson?sdisease(PD)isthesecondmostcommonneurodegenerativediseaseassociatedwithaging.The diseaseischaracterizedbymotorsymptomsattributedtothelossofmesencephalicdopaminergicneuronsand theirinnervationtothebasalgangliamacrocircuit.InpatientsandanimalmodelsofPD,thismacrocircuit exhibitsaberrantactivitypatternsincludingsynchronous,rhythmicburstingofneuronsintheexternalglobus pallidus(GPe).However,thefactorsthatshapethesesynchronousandtemporallystructuredeventsinPD remainunknown.ItisouroverarchinghypothesisthatGABAergicinputsshapetheactivitylevel,pattern,and synchronyofbothparvalbuminandNpas1neuronswithintheGPe.Usingcellandcircuitspecifictools,we willinvestigatetheconnectivityofstriatalinputsandlocalcollateralinputstoparvalbuminandNpas1neurons within the GPe and how this connectivity becomes altered in the chronic 6OHDA lesion model of PD. Furthermore,wewilldeterminehowparvalbuminandNpas1neuronsandtheirstriatalinputsareinvolvedin motor function and dysfunction. The proposed experiments capitalize on a combination of cuttingedge approachesthatwillovercomeobstaclesthathadimpededprogressuntilnow.Theseapproachesincludeviral genedelivery,Creloxrecombination,optogenetics,chemogenetics,electrophysiology,andfiberphotometry. Additionally, anatomical, analytical, and computational approaches will be used to help interpret research findings. The successful achievement of these aims will significantly advance our understanding of the mechanismsunderlyingPDand,indoingso,promotethedevelopmentofnewtherapiesforPDpatients.